Homologous recombination (HR) is essential for repairing double-strand breaks (DSBs) created by DNA replication failure, ionizing radiation, and other damaging agents. However, limiting recombination between the abundant, repetitive sequences dispersed throughout all eukaryotic genomes is crucial to protecting against genome rearrangements. Such rearrangements have been linked to cancer in humans. The yeast two-hybrid system will be used to identify potential interactions between DNA repair proteins involved in attenuating recombination between short repeats and proteins required for HR. Various mutant alleles will be screened in attempt to identify regions of these proteins that are important for their interaction. Recombination assays will be used to examine the effects of potential changes in these interactions on restricting recombination. Fluorescence microscopy will be used to attempt to visualize how these mutations affect colocalization of the proteins to the ends of broken DNA molecules, which may be important for restricting recombination. These studies should provide insight into the physical basis for limiting recombination between repeated sequences, which is an important factor in of the maintenance of genome stability and cancer avoidance.